JPH0349262B2 - - Google Patents

Description

Claim 1: A flexible container 12 containing a liquid diluent therein and having a discharge outlet 20; a drug vial storage capsule 22 connected to the flexible container 12; The drug vial storage capsule 22 has a support means 3 for movably supporting a drug vial 36 containing therein a drug to be mixed with the liquid diluent.
2 to 35, 62, and a pressing means 28 for moving the drug vial 36 towards the flexible container 12 in the axial direction within the capsule 22, the flexible container 12 and the drug vial storage capsule 22 are interconnected by conduit means 52, 52a, 54, said conduit means 52, 52
a, 54 selectively establish communication between the flexible container 12 and drug vial communication means 55, 66 that establish communication with the interior of the drug vial in response to axial movement of the drug vial 36; A closed drug mixing and discharging device characterized in that it comprises flexible container communication means 53, 58.

2. The device of claim 1, wherein the flexible container 12 comprises a sealed vinyl container, and the discharge outlet 20 is at the bottom of the container.

3. The capsule 22 has a relatively rigid bottom 23 and a side wall 24, and the pushing means 28 has a relatively rigid bottom 23 and a side wall 24.
Apparatus according to claim 1 or 2, comprising a flexible push member 28 sealed to the top of the device, said flexible push member 28 being substantially deformable to permit manual downward movement thereof. .

4 The flexible pressing member 28 has a flat central portion 4
4. The device of claim 3, including a plurality of pleats 44 surrounding the flexible push member 28, the flexible push member 28 being sealed to the side wall 24 adjacent its outer periphery.

5. Device according to claim 3 or 4, in which the flexible push member 28 has a generally circular contour and the capsule 22 is provided with means 29, 30 allowing the capsule 22 to be suspended.

6. The drug vial 36 comprises a standard glass drug vial bottle 36 with a pierceable stopper 40 stopped by a metal band 42, and the drug vial communication means 55, 66 allow the vial 36 to pass onto the spikes 55, 66. 6. A device according to any one of clauses 1 to 5, comprising spikes 55, 66 for piercing the stopper 40 when moved.

7. The capsule 22 has a bottom 23 and a side wall 24, and the support means 32 to 35, 62 are attached to the capsule 22.
7. The device according to any one of clauses 1 to 6, comprising a plurality of legs 32-35, 62 extending inwardly from the base.

8. The device of claim 7, wherein the legs 32-35, 62 extend upwardly from the bottom 23 of the capsule 22.

9. The device of claim 7, wherein the legs 32-35 extend radially inwardly from the sidewalls of the capsule 22.

10 The flexible container connection means includes a rupture member 5 that prevents fluid flow unless the rupture member 58 is ruptured.
10. A device according to any one of the preceding clauses, wherein the tube-like part 53 comprises a tube-like part 8.

11. The capsule 22 comprises a relatively rigid plastic housing, and the pushing means 28 comprises a plastic bellows cap 28 sealingly covering the plastic housing, the plastic bellows cap 28 being adapted to allow manual downward movement thereof. 11. A device according to any one of clauses 1 to 10, which is substantially deformable.

12 the flexible container 12, the capsule 22,
12. A device according to any one of clauses 1 to 11, wherein the conduit means 52, 52a, 54 and the communication means 55, 66, 53, 58 have a sterile interior to render the interior of the drug mixing and discharging device sterile.

TECHNICAL FIELD The present invention relates to a novel closed drug release system that allows safe and easy reconstitution of drugs immediately before use.

BACKGROUND OF THE INVENTION Many drugs are mixed with a diluent before being delivered intravenously to a patient. The diluent can be, for example, a dextrose solution, saline or water. Many such drugs are supplied in powder form and packaged in glass vials. Other drugs, such as some used in chemotherapy, are packaged in glass vials in liquid form.

Powdered drugs can be reconstituted in a well-known manner utilizing a syringe used to inject a liquid into a vial for mixing, which ultimately draws the mixed solution out of the vial. When a drug must be diluted prior to release to a patient, the drug is often injected into a diluent container, which can then be connected to a dosing set for delivery to the patient. More specifically, diluents are often packaged in glass bottles or in flexible plastic containers such as those sold under the names Minivac and Viaflex by Travenol, Laboratories, Inc. of Deerfield, Illinois. packaged. These containers have a dosing port for connection to a dosing set that releases the contents from the container to the patient. The drug is typically added to the container through an injection site on the container.

Drugs can be packaged separately from diluents for a variety of reasons. One of the most important reasons is that certain drugs cannot retain their potency when mixed with diluents and therefore cannot be stored for substantial periods of time. In some cases, the drug and diluent may not remain mixed for a significant length of time. Additionally, because many companies that produce drugs are not in the business of providing packaged medical fluids for intravenous delivery, drugs are often packaged separately from the diluent.

Therefore, a doctor, nurse, pharmacist or health care worker must mix the drug and the diluent.
This presents a number of problems. Restore operations take time. The operator must have prestart diluent and syringe available. Powdered drugs often cake at the bottom of the vial. Thus, when injecting a liquid from a syringe into a vial,
The contact area between the liquid and the powdered drug may initially be quite small, making the mixing operation even more time-consuming. Due to limited vial volume, increasing drug concentrations in the diluent make the reconstitution process more difficult to complete. The operator would try to solve this by repeatedly injecting the solution into the vial, mixing the solution, and aspirating, but this would result in extra injections and syringe movement that increases the chance of contamination. Requires. Also, it is often difficult to remove the entire amount of drug and/or diluent from the vial, thereby increasing the time required to perform the reconstitution operation.

The reconstitution operation should preferably be carried out under aseptic conditions. In addition to such requests that legitimately cause operators to be more careful and time-consuming,
Maintaining sterile conditions is often difficult.
In some cases, a laminar flow hood is required under which the restoration operation is carried out.

Some drugs, such as certain chemotherapeutic agents, are toxic. Exposure of operators to such agents during restoration is dangerous, especially if operators handle such agents on a daily basis and are exposed to them repeatedly.

One of the other issues is that the diluent container must be labeled with the drug it was injected with, or at least the name of the patient who is to release it, so restoration will not know which container contains which drug. provides a source of confusion about

It can be seen that a closed system for separate storage of drug and diluent would be most beneficial. However, several facts have until recently prohibited such closed systems from being commercially viable and on a reasonably inexpensive basis. One factor that has made manufacturing difficult in closed systems with separate selectively communicating compartments for drug and diluent has been sterile operation. As an example, in the case of a diluent in a flexible plastic container, the container containing the diluent is sterilized by steam sterilization or autoclaving. However, the heat generated during such sterilization operations will destroy the efficacy of many drugs. On the other hand, other sterilization means, such as the use of ethylene oxide gas, may be harmless to the drug, but may be harmful to the diluent. A system for separately sterilizing drug and diluent and combining the two components into a single container with separate compartments for separate storage after sterilization is disclosed in the ``Sterilized No. 365,940, in the name of William Schunel entitled "Liquid Mixing System.

These considerations should be taken into account if there is no means to protect the drug and diluent during different sterilization steps, the system should be constructed by combining separate drug and diluent containers after they have been sterilized separately. request something. This requires the creation of a sterile or at least sterile connection between the two containers. Sterile connectors are described, for example, in U.S. Pat. No. 4,157,723;
It is known as shown in No. 4265280 and No. 4325417. The connectors disclosed therein provide highly reliable connections. However, they use a separate radiant energy source for making the connection and therefore a power supply to operate the energy source.

One of the other requirements for such a closed system is that
Water vapor transmission from the container containing the diluent to the container containing the powdered drug must be prevented. As previously discussed, storage of some powdered drugs in one place with liquids, even in small amounts, destroys drug efficacy. Such a closed system must also be constructed in a manner that facilitates easy and thorough mixing of drug and diluent.

U.S. Patent Nos. 4,410,321 and 4,411,662 include
A closed drug release system is disclosed in which the drug and diluent are stored separately and selectively mixed under aseptic conditions. In the illustrative embodiment, a sterile coupling containing a permanently attached molded joint is used. However, in some cases it is desirable to avoid the use of permanently attached molded joints as part of a sterile coupling. For this reason, we
Inherits most of the benefits of the systems disclosed in U.S. Pat. Nos. 4,410,321 and 4,411,662, but avoids the use of permanently attached molded joints and
We have developed a closed drug release system that allows safe and easy reconstitution of the drug immediately before use, and is simple to construct and easy to manufacture.

DISCLOSURE OF THE INVENTION According to the present invention, a liquid diluent is contained therein;
and a flexible container having a discharge outlet; and a drug vial storage capsule connected to the flexible container, the drug vial storage capsule having therein a drug to be mixed with the liquid diluent. a support means for supporting the drug vial in an axially movable manner; and a pressing means for moving the drug vial toward the flexible container in the axial direction within the capsule, the flexible container and the drug vial The storage capsule is interconnected by conduit means, the conduit means being responsive to axial movement of the drug vial to establish communication with the interior of the drug vial, and the flexible container. A closed drug mixing and delivery device is provided comprising a flexible container communication means selectively establishing communication with the container.

In an illustrative embodiment, the coupling means includes a rupture member that prevents fluid flow unless the rupture member is ruptured.

A further detailed description of the invention is provided in the following description and claims, and is illustrated in the accompanying drawings.

[Brief explanation of drawings]

FIG. 1 is a perspective view, partially cut away for clarity and showing an open capsule for clarity, of a closed drug delivery system constructed in accordance with the principles of the present invention.

FIG. 2 is a cross-sectional view taken along the plane of line 2--2 of FIG. 1 but showing the top of the capsule in its normally sealed position.

FIG. 3 is a cross-sectional view similar to FIG. 2, but showing a drug vial in motion.

FIG. 4 is a cross-sectional view similar to FIG. 2, but showing a modified embodiment of the invention.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS Referring to FIGS. 1 and 2, a drug delivery system 10 is shown therein. system 10
includes a flexible container 12 preferably fabricated from a sheet of flexible plastic (e.g. polyvinyl chloride) having peripheral seals 13, 14, 15 and 16 forming a compressible chamber 18. Chamber 18 has a liquid diluent therein, such as dextrose solution, saline, or water. A discharge outlet port 20 communicates with chamber 18 and extends from the flexible container at its lowest position. A portion of the port 20 is sealed to the container by sealing the lower ends 21 of the plastic sheets to each other and around the port 20.

A plastic capsule 22 is connected to the flexible container. Capsule 22 has a generally cylindrical shape with a bottom 23, sidewalls 24, upper rim 26, and has a pleated top cap 28 and generally D-shaped hanger members 29,30. The capsule base 23, side walls 24, rim 26, and hanger members 29, 30, which are generally made in a circular shape, are formed into a one-piece molded structure, while the pleated cap 28 is formed separately and the rim 26 is formed later. is joined to. Although cap 28 is shown not attached to rim 26 in FIG. 1, in use cap 28 is connected to rim 26 and the drug delivery system is connected to a closed, sterile system as discussed below. Become a system.

The bottom 23 and side walls 24 of the capsule 22 are relatively rigid and support means in the form of four legs 32, 33, 34 and 35 extend inwardly from the bottom of the side walls 24 of the capsule. Legs 32-35 support standard glass drug vials 36 located within the capsule. The vial 36 contains a powder or liquid drug and, as is customary, includes a neck 38 extending to a rubber stoppered end 40, the rubber pierceable stopper being secured by a metal band 42.

Cap 28 is generally circular and includes three concentric pleats 44 surrounding a flat central portion 46. The outer peripheral portion 48 of the cap 28 is sealed to the capsule rim 26 by sonic welding or by the use of heated dies. The cap 28 overlies and is a short distance away from the bottom 50 of the vial 36, so that when the flat portion of the cap 28 is manually pushed, it moves the vial 36 downwardly, as will be explained in more detail below.

Capsule 22 includes an outwardly extending tube 52 surrounding a plastic hub 57. Hub 57 is overmolded around a one-piece stainless steel needle 52 with a spiked tip extending into the center of capsule 22. The other end 56 of hollow needle 54 extends into chamber 18 near the top of the chamber. The lower part of the needle 54 is surrounded by a tube-shaped portion 53 of a plastic breaking member 58. Tube-shaped portion 53 of breaking member 58
is secured to the needle 54 by an interference fit between the needle and the tubular portion 53, or by the use of adhesive, or by an interference fit and the use of adhesive.

Breaking member 58 includes a tubular portion 53, a closed breaking section 60, and a rib 63 similar to the breaking member disclosed in U.S. Pat. No. 4,340,049. When broken at section 60, tubular portion 53 will open at its bottom.

The breaking member 58 is surrounded by a sleeve 52a with two side ports 61 located relatively high up in the chamber 18. Sleeve 52a is connected to container 12 by a heat seal 14 that secures the outer sheet forming container 12 when heat seal 14 is applied.

The use of a side port 61 located relatively high up in the chamber 18 towards the seal 14 increases the size of the flow path for gaseous or liquid fluid entering the chamber 18 through the needle 54 and thus Liquid or air passing through end 56 of tube 52a can exit from end 65 of tube 52a;
Or it can exit from port 61. Second
Additionally, port 61 allows air within chamber 18 to easily return into vial 36. By placing the port 61 relatively high up in the chamber, less air remains in the chamber than during manufacturing. In other words, the container 12 can be manufactured to a high liquid level. Therefore, the tube 52a
A side port 61 therein allows air to return from container 12 into vial 36 to pressurize the liquid in vial 36 for return to chamber 18 .

Referring now to FIG. 3, the process of mixing the drug in vial 36 with the diluent in chamber 18 is as follows. To deform the cap 28 downwardly as shown in FIG.
Thumb pressure is applied to the flat central member 46 of. This will push vial 36 downward as shown. The legs 32-35 provide elasticity to allow this downward movement so that the spike 55 will pierce the rubber stopper at the end 40 of the vial 36. The operator then manually bends the breaking member 58 and breaks it along the breaking section 60 to open the passageway, thereby opening the hollow needle 54.
will communicate with the interior of chamber 18 and the interior of vial 36. The flexible container 12 can then be compressed to force the diluent into the vial 36, and the diluent will mix with the drug located within the vial 36.

FIG. 4 shows that in the embodiment of FIG. 4, the four legs (only three of the legs are shown)
6, except that they extend upwardly from the bottom 23 of the capsule 22 to support the
Figure 3 illustrates a closed drug delivery system 10' similar to the embodiment of Figure 3; Additionally, instead of using a hollow stainless steel needle as in the embodiment of FIGS. 1-3, a hollow rigid plastic pike 64 is used. One end 66 of the spike 64
communicates with the interior of the capsule 22, while the spike 6
The other end 68 of 4 communicates with the interior of chamber 18 when the breaking member is broken.

In the manufacture of the system illustrated in FIGS. 1-3 and the system of FIG. The empty capsules 22 are steam sterilized. Steam sterilized unit, cap 28 and vial 36
is placed in a chamber, which is then gas sterilized. Once this gas sterilization has been performed, the vial 36 is inserted into the capsule and the cap 28 is inserted into the lip 2.
6 by sonic welding or by the use of heated dies. Use a glove box to work with vials and connect caps.
Or it can be performed by a worker in a clean suit.

In the specific example described above, the pleated cap 28 of the capsule 22 serves as a pushing means for moving the vial 36 toward the flexible container 12 in the axial direction within the capsule, and also allows the vial 36 to be moved in such an axial direction. The supporting means supporting the capsule 22 are the legs 32-35. Furthermore, capsule 22
The conduit means interconnecting the flexible container 12 and
Tube 52, sleeve 52a and hollow needle 54
In the specific example of FIGS. 1 to 3, the drug vial communication means is the spike 55 of the hollow needle 54, and the fourth
It will be appreciated that in the illustrated embodiment it is a plastic spike 66 and that the flexible container communication means is a tube-shaped portion 53 which is normally closed by a breaking member 58.

The device of the present invention configured as described above not only enables easy aseptic mixing of the drug in the vial 36 and the liquid diluent in the flexible container 12 in a closed system, but also allows for flexible mixing after mixing. The outlet 20 of the container 12 can be connected to a conventional drug set and used directly for administering the drug to a patient. Furthermore, compared to the systems disclosed in U.S. Pat.
Rigid capsules provide benefits such as protecting the drug vial from impact damage.

It can be seen that a sterile, closed drug release system has been provided that does not require permanent molded joints and allows safe and easy reconstitution of the drug immediately prior to use.

Although illustrative embodiments of the invention have been illustrated and described, various modifications and substitutions can be made by those skilled in the art without departing from the novel spirit and scope of the invention.